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前立腺癌103例を対象に, 24週で被験薬TAP-144-SR(3M)(TAP-144として11.25mg含有)2回投与(A群)と, 対照薬TAP-144-SR(1M)(TAP-144として3.75mg含有)6回投与(B群)に無作為割付した.血清中テストステロン濃度の去勢レベル維持率は両群とも100%であった.前立腺癌取り扱い規約中の「前立腺癌の非観血的治療効果判定基準」にしたがった総合効果の維持率は, A群80.4%, B群84.0%と有意差はなかった.A群のAUC1～12W実測値の平均値はB群の77.0%であった.安全性は両群とも特に問題はなかった.TAP-144-SR(3M)は, 長期にわたる前立腺癌治療に適した薬剤であることが示された, A randomized, multicenter, double-blind, parallel-group study was conducted in order to evaluate the hormonal kinetics, pharmacokinetics, efficacy and safety of TAP-144-SR (3M) a three-month sustained-release injectable preparation of leuprorelin acetate, a highly active luteinizing hormone-releasing hormone (LH-RH) derivative by comparing the treatment with two subcutaneous doses of the test medication TAP-144-SR (3M) and the treatment with six subcutaneous doses of the reference medication TAP-144-SR (1M), a 1-month sustained-release injectable preparation. Study participants were 103 patients with prostate cancer in whom a stable anti-tumor effect had been obtained with Leuplin Injection 3.75. The hormonal kinetics revealed that the proportion of the patients "maintaining the castration level of serum testosterone (maximum serum testosterone level during treatment below the castration level [100 ng/dl])" was 100% in both treatment groups. With regard to the efficacy, the proportions of the patients in whom the anti-tumor effects (> or = Stable) of the baseline treatment prior to the initiation of the treatment with the study medication were maintained during the study treatment period (6 months) were comparable; 84.0% with TAP-144-SR (1M) and 80.4% with TAP-144-SR (3M). On evaluation of the pharmacokinetics, the mean value of AUC1-12w of the serum TAP-144 concentration (including the metabolite M-I) for the treatment with TAP-144-SR (3M) was 77.0% that of the treatment with TAP-144-SR (1M). Adverse events were similar in the subjects on TAP-144-SR (3M) and in those on TAP-144-SR (1M). There existed no big differences in kind, incidence or time of occurrence of adverse events between two groups. TAP-144-SR (3M) showed no clinically relevant findings in particular. These results indicate that one dose of TAP-144-SR (3M) is comparable to three doses of the already approved Leuplin injection 3.75 in serum testosterone level-inhibitory effect, efficacy and safety. Hence, it is considered that TAP-144-SR (3M) is a drug suitable for treatment of prostate cancer over a prolonged period of time.

日本人前立腺癌患者40例(新鮮例20例, 切替例20例)を対象に, 10.8mgデポ1筒を単回皮下投与し, 有効性及び安全性を評価した.その結果, 薬力学的効果では, 新鮮例全例の血清テストステロン濃度は投与4週後迄に去勢域値以下へ抑制され, 12週後まで維持された.新鮮例の抗腫瘍効果を評価した結果, 投与12週後の奏効率は90.0%で, PSAの正常化率は75.0%であった.副作用は27例に見られ, ほてりが20.0%と最も高かった.10.8mgデポの投与結果を3.6mgデポの臨床成績と比較した結果, 有効性及び安全性は3.6mgデポと同様と考えられた.新鮮例で薬物血中濃度を測定した結果, 投与2時間後に最高血清中濃度に達し, 72時間後迄に速やかに減少した.前立腺癌患者に単回皮下投与することで, 有効性は12週間持続し, 3.6mgデポと同様の良好な忍容性を認めた, Pharmacodynamics (PD), anti-tumor effects, safety and pharmacokinetics of a 3-month formulation of goserelin (Zoladex (R)LA 10.8 mg depot: "10.8 mg depot") were investigated in a collaborative multicenter study. Study participants were 40 Japanese patients with prostate cancer comprising 20 untreated patients and 20 switch patients who had been receiving Zoladex(R) 3.6 mg depot for 3 months or longer. Serum testosterone levels, serum LH levels, prostate-specific antigen (PSA) levels and drug concentrations were measured until 12 weeks after a single subcutaneous dose of 10.8 mg depot. Anti-tumor effects were evaluated by means of changes in the tumor lesions and the PSA levels at 12 weeks. After administration to the untreated patients, 10.8 mg depot reduced serum testosterone to the castrate range within 4 weeks and the reduction was maintained for up to 12 weeks. In the switch patients, serum testosterone suppression that had been produced by previous treatment with Zoladex(R) 3.6 mg depot was maintained for up to 12 weeks following 10.8 mg depot administration. The anti-tumor effect at 12 weeks was 90.0% including partial response cases. The ratio of PSA normalization at 12 weeks was 75.0%. Fifty-seven adverse reactions were observed in 27 of the 40 patients (67.5%), but none were clinically significant. Although a disease flare presented as urinary retention in 1 of the untreated patients, all patients completed the study. Serum goserelin was detected up to 12 weeks after the administration of 10.8 mg depot. In conclusion a single dose of 10.8 mg depot showed a satisfactory PD-effect and brought about clinical efficacy persisting for at least 12 weeks and was well tolerated in patients with prostate cancer.

1)初期化学療法のみの57例中CRは24例, PRは33例, 再燃は8例, 長期生存(NED)は52例であった. 2)救済化学療法の16例中CRは1例, PRは12例, PDは3例, 再燃は3例, NEDは11例であった. 3)残存組織が壊死に達した24例のNEDは96%, 成熟奇形腫(6例)では100%に対して, 残存癌(13例)では54%で予後不良であった. 4)腫瘍マーカーが正常化した32例中8例に残存癌が認められたことから化学療法終了時に, 残存癌の有無を予測するのは困難で, 適切な時期の救済外科療法が重要である. 5)救済外科療法後の再発や, 手術不能例の難治性精巣腫瘍19例の治療成績は, 集学的治療にも拘わらずNEDが9例であった, Since 1980, 73 patients with advanced testicular cancer have been treated with chemotherapy and 43 patients received post-chemotherapy (salvage) surgery. The median age of all patients was 31 years old, ranging from 17 to 63 years. The histology of the primary testicular tumor was pure seminoma in 23 patients and non-seminoma in 50 patients. According to the Japan Urological Association classification, 38 patients were classified as stage II and 35 patients as stage III. As first-line chamotherapy, 52 patients were treated with PVB regimen (cisplatin, vinblastin, bleomycin), 16 patients with PEB (cisplatin, etoposide, bleomycin) and 5 patients with VAB-6 (vinblastine, actinomycin-D, bleomycin, cisplatin, cyclophosphamide). Thirty (41%) of the 73 patients achieved a complete response (CR) with chemotherapy alone and 63 (86%) achieved no evidence of disease (NED) with salvage treatment. As second-line chemotherapy, 16 patients were treated with PE (cisplatin, etoposide), or VIP (etoposide, ifosfamide, cisplatin) or VeIP (vinblastine, ifosfamide, cisplatin). One of the 16 patients achieved CR and 11 (69%) patients achieved NED. As salvage surgery, retroperitoneal lymphnode dissection (RPLND) was performed in 22 patients, RPLND with thoracotomy in 7 cases and thoracotomy alone in 4 cases. Necrosis was found in surgical specimens of 24 (56%) patients, mature teratoma in 6 (14%) and residual cancer in 13 (30%). Ninety-six percent and 100% of the patients with necrosis and mature teratoma survived with NED, respectively, but only 54% of the patients with residual carcinoma survived despite further treatment. Residual cancer was still found in 8 of the 32 (25%) marker normalized cases. Residual cancer could not reliably be predicted or discriminated from necrosis or mature teratoma by the prognostic criteria. Therefore, salvage surgery remains essential in the treatment of advanced testicular cancer.

Despite the generally high cure rate in patients with metastatic testicular cancer, 20% to 30% of treated patients will become candidates for salvage chemotherapy. We reviewed the recent salvage chemotherapy trials of refractory diseases. CPT-11 is a new derivative of camptothecin and has activity in a variety of solid tumors. We evaluated the antitumor effect of combination chemotherapy using CDDP and CPT-11 against refractory testicular cancer. Fourteen patients who failed to achieve complete remission with salvage chemotherapy were treated with combination chemotherapy with CPT-11 and CDDP or 254-S (nedaplatin) as third line chemotherapy. Six patients remain alive and disease-free and 5 patients died of disease. The combination of CPT-11 and either CDDP or nedaplatin was significantly more effective than other salvage therapy regimens such as VIP. Paclitaxel, ifosfamide, etoposide regimens were also effective in patients with refractory testicular tumors. We concluded that these combination regimens demonstrated significant activity against refractory testicular tumor and further investigation is warranted.

1)f-PSAとc-PSA測定系とも各抗原を特異的に測定し, t-PSA測定系はf-PSAとc-PSAを1:1の割合で測定していた. 2)f/t%とf/c%は共にPCaにおいてA1やB0のような早い病期からnon PCaと有意差が認められた. 3)t-PSAとc-PSA及びf/t%とf/c%のROC曲線における差は殆ど認められず, c-PSAの診断上の有用性はt-PSAと同等と思われた.f-PSA単独では有用性が認められなかった. 4)t-PSAが4～10ng/mlの検体においてはf/t%とf/c%がPSA-Dと同様に前立腺癌の診断に有効であった. 5)前立腺体積40ml以上でt-PSAが10ng/ml以下では癌でない確率が高い, We studied the clinical significance of serum prostate specific antigen (PSA) ratio: free-PSA/total-PSA and free-PSA/complex-PSA to discriminate between prostate cancer (PC) and prostate benign disease (non-PCa) by using total-PSA, alpha 1-antichymotrypsin complexed (complex)-PSA and free-PSA enzyme-linked immunosorbent assay (ELISA) kits newly developed at EIKEN Chemical Co, Ltd. Fre-PSA and complex-PSA ELISA kits demonstrated high sensitivity and specificity. Total-PSA ELISA kit also demonstrated equimolarity for free-PSA and complex-PSA. On the total-PSA range of 4-10 ng/ml, free-PSA/total-PSA% (f/t%) and free-PSA/complex-PSA% (f/c%) were very useful to discriminate between PCa and non-PCa by receiver operating characteristic curve analysis as well as PSA density (PSA-D) but not free-PSA level. F/t% and f/c% were even useful to discriminate early stage PCa (i.e. A1 or B0) from non-PCa by the Mann-Whitney U-test.

前立腺肥大症の診断で手術を施行し, 組織診断で良性であった179症例と癌が検出された23症例の特性をretrospectiveに検討した. 1)前立腺肥大症症例において前立腺体積とPSA値は有意に相関した. 2)Tla癌の特性は前立腺肥大症と差はなく, 鑑別はできなかった. 3)Tlb癌のPSA値, PSAD値は前立腺肥大症に比べ有意に高く, 前立腺体積, 切除重量は有意に小さかった. 4)Tla, Tlb癌の鑑別におけるPSAのcut-off値としては8ng/mlが, PSADのcut-off値としては0.25ng/ml/mlが適当であった.またこの時見落とされる癌の多くは鑑別困難なTla癌で, 予測される癌の多くはTlb癌であった. 5)PSADを用いることでPSAより特異性が改善された, The clinical significance of preoperative prostate specific antigen (PSA) and PSA density (PSAD) in distinguishing stage T1a and T1b prostate cancer from benign prostatic hyperplasia (BPH) was studied retrospectively in men who had undergone surgery for BPH. A total of 202 clinically BPH patients underwent transurethral resection of prostate (TURP) or retropubic prostatectomy, and histopathological findings were BPH in 179 patients, T1a cancer in 10 patients and T1b cancer in 13 patients. The T1a cancer group was similar to the BPH group in all parameters. The PSA and PSAD values in the T1b cancer group were significantly higher than those in the BPH group (P < 0.001). Prostate volume and amount of tissue resected in the T1b cancer group were significantly smaller than those in the BPH group (p < 0.001). The cut-off values of PSA and PSAD were examined with T1a and T1b cancer as a positive control and histologically proven BPH as a negative control. When 8.0 ng/ml was used as the PSA cut-off value, the sensitivity was 65% and specificity was 70%. When 0.25 ng/ml/ml was used as the PSAD cut-off value, the sensitivity and specificity were 65% and 75%, respectively. PSAD was useful for improving the specificity. Almost all the cases undetected by using both cut-off values were of T1a cancer. The receiver operating characteristics curve demonstrated that at any point, PSAD was a better detector for distinguishing T1a, T1b cancer from BPH, focusing especially in the range of PSA level between 6.0 and 10.0 ng/ml. These findings suggest that PSA and PSAD are useful parameters in distinguishing T1b cancer from BPH before surgery.

75歳以下の病期C69例について解析した. 1)非再発率の検討より, 高, 中分化癌かつT3a～c(低リスク群)と低分化癌或いはT4a(高リスク群)の2群に分けることができた. 2)前立腺全摘除術+内分泌療法は29例, 放射線療法+内分泌療法21例, 及び内分泌療法単独19例で, 放射線療法群に低分化癌が多い傾向があり, 内分泌療法単独群にT4aのhigh stage症例が多かった. 3)低リスク群で前立腺全摘除術による再発, 再燃症例はなく, 前立腺全摘除術の最もいい適応と考えられた. 4)高リスク群では前立腺全摘除術は放射線療法に比較し再発, 再燃率は高く, 放射線療法が適応である, Of the 69 patients with clinical stage C prostate cancer under 75 years old and with good performance status between 1986 and 1995, 29 underwent radical prostatectomy combined with endocrine therapy, 21 underwent radiation therapy combined with endocrine therapy and remaining 19 patients were treated by endocrine therapy alone. The median followup was 44 months (range 4 to 122). Radical prostatectomy resulted in progression-free rates of 79% and 61% at 5 and 10 years, respectively. Progression-free rates were lower in patients with lymph node metastasis or positive surgical margins. In patients with clinical stage T3a-c and well or moderately differentiated tumor, radical prostatectomy resulted in a progression-free rate of 100% at 5 years. However, in patients with clinical stage T4a or poorly differentiated tumor, radiation therapy resulted in a better progression-free rate than radical prostatectomy. These findings suggest that patients with clinical stage T3a-c and well or moderately differentiated tumor will benefit from radical prostatectomy combined with endocrine therapy and that radiation therapy well be effective for advanced diseases.

結節性硬化症の合併は認めない.腹部超音波検査にて, 右腎の中部外側に高エコーを呈する腫瘤を, 下極付近に前者よりも更に高エコーを呈する腫瘤と指摘され当科受診.CT, MRI, 血管造影にて, 右腎中部外側の腫瘤は腎細胞癌と術前診断された.1990年3月経腹膜的根治的右腎摘除術を施行, 中部外側の腫瘍は腎細胞癌, alveolar type, common type, clear cell subtype, G1と, 下極付近の腫瘍は腎血管筋脂肪腫と病理診断された.術後経過は良好で, 術後61ヵ月再発転移を認めない, Coexistence of renal cell carcinoma and angiomyolipoma in the same kidney is rare. A 54-year-old woman without tuberous sclerosis was admitted for further examination of incidental renal masses on ultrasonography. Computerized tomography revealed a 17-mm high density mass in the mediolateral portion of the right kidney and a 5-mm low density mass near the right lower pole. Because the former mass showed a typical tumor pattern on selective renal angiography and the latter mass was strongly hyperechoic on ultrasonography, a clinical diagnosis of renal cell carcinoma and angiomyolipoma was made. A right radical nephrectomy confirmed the preoperative diagnosis. She has been followed for 61 months with no recurrence.

排尿困難, 腹部膨満を主訴とした60歳男で, 直腸内指診で鵞卵大の前立腺を触れ, 表面は平滑で, 弾性軟であった.血清前立腺特異的抗原濃度は78ng/mlに上昇していた.骨盤CT及びMRIで大きい前立腺, 直径9cmの嚢胞状腫瘤, 及び内腸骨リンパ節腫脹を認めた.前立腺及び嚢胞の針生検で低分化腺癌を認め, 嚢胞内溶液は血性で, 細胞診は陰性であった.T4N3M0の前立腺癌と診断された.内分泌療法を行った.初診後4年の現在, 排尿障害もなく経過良好である, A 60-year-old man was admitted to our hospital with the chief complaints of dysuria and sense of abdominal fullness. On digital rectal examination, an enlarged prostate with a smooth surface and elasticity was palpated. The concentration of prostate specific antigen (PSA) was elevated to 78 ng/ml. Pelvic computed tomographic (CT) scan and magnetic resonance imaging (MRI) revealed a large prostate, 8 cm in diameter, with a cystic mass, and extra-iliac lymph node swelling. On needle biopsy of the prostate and cyst, the histology was poorly differentiated adenocarcinoma, and the aspirate comprised bloody fluid with a negative test for cytology. He was diagnosed with prostatic cancer of T4N3M0. This is the 19th case of prostatic cancer with cystic formation reported in Japan.

33歳女.腹部膨隆を主訴とし, 腹部超音波検査, DIPと順行性腎盂造影, CT, MRI, 膀胱鏡検査等で, 両側重複腎盂尿管の右上半腎より発生した巨大水腎症と術前診断された.腰部斜切開で後腹膜腔に入ると右上半腎所属の尿管は明らかな腎盂尿管移行部狭窄を伴っており, これにより巨大水腎症が発生したと思われた.尿管異所開口の部位は断定できないが, すくなくとも外尿道括約筋群よりも遠位であると考えられた.巨大水腎とその所属尿管は一塊として摘出され, 巨大水腎の内容量は2, 640mlであった.術後1年目のDIPで良好な経過を取っている, Giant hydronephrosis is an uncommon clinical entity. Even more uncommon is the association of giant hydronephrosis with a double collecting system and ectopic ureter. Here, we report a case of giant hydronephrosis of the bilateral duplex systems associated with ureteral ectopia. The patient underwent upper pole nephrectomy and upper ureterectomy. To our knowledge, only four similar cases have been reported previously.

1)登録症例は16例で, 全例が適格例であった. 2)副作用は16例中8例に認められたが, 軽度で, 臨床上特に問題はなかった.乳房圧痛, 乳房腫脹等の副作用が50mg群で1例, 80mg群で3例及び100mg群で2例に認められた. 3)有効性に関しては, 各投与群の1例ないし2例において, PR以上の抗腫瘍効果が認められた.又, 排尿困難, 排尿痛, 夜間頻尿の改善がみられた. 4)血清中ホルモンでは, LH, FSH, testosterone及びestradiol濃度の上昇が認められた, A phase I study (open trial) of bicalutamide (Casodex), a non-steroidal antiandrogen, was conducted on 16 patients with prostatic cancer (stage C to D). The patients were given 10, 30, 50, 80 or 100 mg of bicalutamide orally daily for 12 weeks. Adverse reactions were observed in 8 out of 16 patients, but almost all were mild. Breast pain, gynecomastia and hot flushes were observed in 6 patients. Adverse reactions regarding liver function tests were observed in 3 patients. These were increased glutamic-oxalacetic transaminase (GOT), glutamic-pyruvic transaminase (GPT), alkaliphosphatase (AL-P) or gamma guanosine 5'-triphosphate (gamma-GTP). However, during or after the treatment period the elevated values were reversed to the pretreatment level. In terms of efficacy, anti-tumor effect was observed in 1 or 2 patients at each dose. Serum concentrations of luteinizing hormone (LH), follicle stimulating hormone (FSH), testosterone and estradiol increased during treatment. Plasma concentrations of the R (-) enantiomer, which has antiandrogenic activity, reached the steady state 6-8 weeks after the initiation of treatment; its apparent plasma elimination half-life observed following repeated administration was 8.4 +/- 1.1 days. In conclusion, bicalutamide (10-100 mg od) is considered to be tolerated well enough to be administered to patients with prostatic cancer and has shown evidence of anti-tumor effect.

ビカルタミド1日1回50mg群, 80mg及び100mgを12週間投与する3群比較の無作為化非盲検試験を実施した. 1)登録症例は124例で, 適格例は122例であった. 2)総合効果における奏効率は50mg群, 80mg群及び100mg群でそれぞれ50.5%, 61.0%及び53.7%であった. 3)PSAに対する奏効率は50mg群, 80mg群及び100mg群でそれぞれ84.2%, 92.7%及び97.6%であった. 4)副作用発現率は3群ほぼ6割で副作用による中止例は80mg群の1例のみで, 安全度において3群間に有意差はなかった.主な副作用は乳房腫脹, 乳房圧痛等であった, To investigate the efficacy and safety of bicalutamide (Casodex(R)) with its clinically recommended dose, the randomized early phase II study was performed in 124 patients with prostatic cancer (stage C, D). The patients were given 50, 80 or 100 mg of bicalutamide orally once a day in fixed doses for 12 weeks ; 122 patients were eligible for evaluation. The overall response rate was 50.0% (20/40); 61.0% (25/41) and 53.7% (22/41) in the 50 mg, 80 mg and 100 mg groups, respectively. The response rate in prostate lesion, bone and lymph node metastases was slightly higher in the 80 mg group than in the 50 mg and 100 mg groups. The proportion of patients showing a response with regard to serum PSA (CR and PR) was 84.2, 92.7 and 97.6% in the 50, 80 and 100 mg groups, respectively. The incidence of adverse reactions was 65.0, 61.0 and 61.0% in the 50, 80 and 100 mg groups, respectively, and there was no significant difference in overall safety rating in the three groups. Frequent adverse reactions were gynecomastia and breast pain. Only one patient in the 80 ing group was withdrawn due to shortness of breath. Serum concentrations of LH, testosterone and estradiol increased significantly after treatment. Bicalutamide was concluded to be effective and well tolerated in patients with prostatic cancer, and its recommended dose was 80 mg once daily.

1)RCCの腫瘍径が80mm以下の摘除された43腎の連続全割面を検索し, 3例に微小のsatellite RCCを, 4例に良性腫瘍を認めた. 2)主腫瘍径の大きさとsatellite RCCの発見とは, 相関しなかった. 3)主腫瘍とsatellite RCCの距離は, 10～70mmであった. 4)Satellite RCCの発見と主腫瘍のgrade, stage, 脈管侵襲などの各背景因子との関連性は認められなかった, Nephron-sparing surgery was initially limited to the patients with localized renal cancer (RCC) present bilaterally or in a solitary kidney. Recently there is controversy in the indication for partial nephrectomy or enucleation to incidentally defined small RCC with normal opposite kidney. We examined the incidence of multicentricity in 43 kidneys removed for RCC with a diameter of less than 80 mm. The mean diameter of the predominant tumors was 45 mm (range 12 to 80 mm). The kidneys were serially sectioned at 5 mm intervals. Three of 43 kidneys (7%) had multiple RCC. The size of the concomitant tumors ranged from 2 to 15 mm. The multicentricity had no relation to pathological grade, stage, vascular invasion or infiltration pattern. In addition, the other 4 kidneys had 2 adenomas, 1 angiomyolipoma and 1 fibroma. Therefore we observed a 16% incidence of small renal nodules and a 7% multicentricity of RCC in the nephrectomized kidneys with normal opposite kidney.

1964～1992年の間に治療した腎細胞癌患者279例中64例は遠隔転移があり, 55例は根治手術後の再発であった。14例で肺転移を切除したが, 片側転移例は両側転移例に比し生存が有意に良かった。18例で骨転移を切除したが, 予後は非常に不良で, グレード1の1例のみが3年以上生存した。又, 11例中9例でQOL (quality of life)が改善された。副腎転移単独は比較的予後が良かった。脳転移例は全例他の転移があるので, QOL改善の為に切除した。リンパ節転移は一般に予後不良であった。インターフェロンα-シメチジン併用療法施行転移癌25例中, 寛解を認めた9例は非寛解例に比し長く生存した, The prognosis of advanced renal cell carcinoma, especially with metastatic lesions was very poor. We described the outcome of surgical treatment of advanced renal cell carcinoma with metastasis. From 1964 to 1992, 279 cases of renal cancer were treated in the Department of Urology, the Center for Adult Diseases, Osaka. Sixty four cases were with distant metastasis (M1 case) and 55 cases were recurrent after radical nephrectomy (M0-M1 case). Among these 119 cases with distant metastasis, 50 cases were treated by surgical resection. Indication of surgical resection was first to obtain surgical complete regression (sCR), second to improve quality of life (QOL). Lung metastases from 14 patients (M1, 5 cases; M0-M1, 9 cases) were resected. The survival of patients with unilateral lung metastases was significantly better than that of patients with bilateral lung metastases. Bone metastases from 18 patients (7 cases to obtain sCR, 11 cases to improve QOL) were resected. The prognosis of patients with bone metastasis was very poor, and more than a 3-year survival was seen in only patients histopathologically with grade 1. QOL improvement was observed in 9 of 11 patients (82%). Solitary adrenal metastasis showed a relatively good prognosis. Surgical resection of brain metastasis was performed only to improve QOL, because all patients had other metastases. Lymph node metastasis showed in general poor prognosis. Six cases with tumor thrombus extending into inferior vena cava nephrectomized under extracorporeal circulation.(ABSTRACT TRUNCATED AT 250 WORDS)

救済外科療法の施行にあたっては安易な手術適応を避け, 十分な術前化学療法などを行い, 残存病巣を壊死, 奇形腫に導き, 完全切除すべきである。残存癌例に対しては, 術後の再発の危険性が非常に高いため, 十分な術後化学療法が必要である, Twenty-seven patients with advanced testicular cancer underwent cisplatin-based combination chemotherapy and followed by salvage surgery. Complete necrosis and/or fibrosis (necrosis) was found in 12 (44%) operative specimens, mature teratoma in 5 (19%) and residual cancer in 10 (37%) patients. Ten of the 12 (83%) patients with necrosis and all 5 with mature teratoma were rendered disease-free (NED). Only 6 of the 10 (60%) patients with residual cancer were continuously NED. These findings suggest that if carcinoma is found in the resected specimen, further salvage chemotherapy is required. Salvage surgery should be avoided in patients with elevated serum tumor marker levels.

ヌードマウス可移植ヒト精巣腫瘍株を用い, CPT-11とCDDPなどのプラチナ化合物との併用療法により, 抗腫瘍効果の著しい増強がみられることを示した。この結果をふまえ, 4例の難治性精巣腫瘍に対しCPT-11とCDDPや254-Sによる併用療法を行い, 2例でその有効性が示された, The antitumor effects of combination chemotherapies using CDDP and the camptothecin analogue CPT-11 were compared with those of vinca alkaloids or podophyllotoxins, and those of CPT-11 and cisplatinum analogues were also estimated. Two human testicular cancer xenografts (TTSC -2 and TTSC-3) heterotransplanted in nude mice were used. Combination therapy with CPT-11 and CDDP resulted in significant tumor regression and was much more effective than that of CDDP and vinca alkaloids or podophyllotoxin. The combination of CPT-11 and either CDDP or 254-S was significantly more effective than that of CPT-11 and either carboplatin or DWA2114R. Four evaluable refractory testicular cancers were treated with combination chemotherapy with CPT-11 and CDDP or 254-S as third line chemotherapy. Two patients remain alive and disease free and two patients died of disease. We concluded that the present combination is active in refractory testicular cancer.

1)本法は再現性が安定し, 信頼度も高くかつ最小検出感度も高く(0.1ng/ml), その基礎的検討の結果は満足できる。2)日本人健常男性244例(21歳～79歳, 平均46歳)における測定の結果, 平均±S.D.は0.93±0.96ng/mlであった。正常上限を4.0ng/mlとしたとき98%(236/244)が4.0ng/ml以下であった。3)前立腺肥大症を対象として各カットオフ値における感度, 特異性, 正診率を求めたところ, カットオフ8.0ng/mlのとき最大正診率(感度84%, 特異性82%, 正診率83%)を示した。このことより正常と前立腺肥大症およびstage Aを含む早期前立腺癌との鑑別においては正常上限である4.0ng/mlを, 前立腺肥大症と前立腺癌との鑑別においては8.0ng/ml(stage Aの陽性率は66%から33%へ減る)をカットオフとすべきと考えられた, A study of the clinical utility of the IMx PA Dainapack, a new kit for detection of serum prostate specific antigen (PSA) by a fully automated enzyme immunoassay (EIA) system, was conducted. Results concerning reproducibility, dilution linearity and sensitivity were good. The excellent assay performance of this kit, particularly in terms of its high sensitivity (0.1 ng/ml), was confirmed. The upper limit of normal was determined to be 4.0 ng/ml from the mean +/- 3 S.D. (3.79 ng/ml) in healthy male controls (n = 244). Using 4.0 ng/ml as the upper limit of normal, 6 of 244 healthy male controls (2%) were positive. In various urinary diseases, 173 of 192 prostatic cancer (90%) and 46 of 112 benign prostatic hypertrophy (BPH) (41%) cases were positive. In prostatic cancer, the positive rates increased with the advance in clinical stage and in stage A the positive rate was especially high (8 of 12 (67%) were positive). On the other hand, using the BPH group as a negative control, the maximum accuracy rate for prostatic cancer had a cut-off value of 8.0 ng/ml. Thus, 8.0 ng/ml is an appropriate cut-off value differentiating prostatic cancer from BPH while 4.0 ng/ml is the cut-off value between the normal group and those with prostatic cancer (including stage A) and BPH. In the follow-up patients with prostatic cancer, serum PSA values measured by this kit reflected the effectiveness of treatment. The correlations between values obtained with the IMx PA Dainapack and 6 current kits were good (r = 0.93 to 0.99) but the values differed with the kit.(ABSTRACT TRUNCATED AT 250 WORDS)

1)125, 250, 375および500mgの用量の単回経口投与を受けた計11名の患者では副作用を認めなかった。2)375, 750, 1, 125および1, 500mg/日の用量の1日3分割経口投与を連日28日間行ったところ, 1, 500mg/日の投与を受けた4例中1例に胃部不快感, 悪心・嘔吐, 食欲不振の副作用症状を認めた。他の用量を投与された9例では副作用の訴えはなかった。3)臨床検査値の異常は375mg/日群の3例では認められなかったが, 他の用量群で9例中5例にトラスアミナーゼの上昇を認めた。特に, 1, 500mg/日群では評価可能な3例の全例に異常値を見た。4)LHの濃度の有意な上昇を認めた。5)客観的効果が各群において3例中2例に観察された。また, 疼痛, 排尿障害, PSの改善が認められた。6)投与後速やかに吸収され, 大部分が水酸化を受けたOH-フルタミドとして血液中に存在していた。また, 単回投与と比べ, 連日投与後のOH-フルタミドの半減期には大差を認めなかったがCmaxおよびAUCは増加していた。7)第2相臨床試験の試験用量としては, 375mg/日から1, 125mg/日の範囲が望ましいと結論された, A phase I study of orally administered flutamide (a pure anti-androgen) was performed in 26 patients with prostatic cancer. No side effects were observed in 11 patients receiving single doses of either 125, 250, 375 or 500 mg. However, in the daily dosing schedule of 375, 750, 1125 and 1, 500 mg/day doses, where medication was taken in three divided doses, discomfort in the stomach, nausea, vomiting and anorexia were experienced in one of the four patients receiving the highest dose of 1, 500 mg. Nine patients receiving the other doses did not complain of toxic symptoms. Laboratory values did not change in the three patients receiving the lowest 375 mg/day dose, but elevation of transaminase was observed in five of the nine patients given higher doses. This elevation was observed in all the three patients receiving 1, 500 mg/day dose. Among the serum hormone levels, significant increases of luteinizing hormone were observed. As for efficacy, objective responses were observed in two of the three patients in each of the four daily dosing groups. Improvement of pain, voiding obstruction symptoms, and performance status were also observed. Flutamide was found to be absorbed rapidly and to exist as a hydroxylated form (hydroxy-flutamide) in the plasma. The half-life of hydroxy-flutamide was similar in the single and daily administration, but the peak concentration and area under the concentration versus time curve in the daily administration became greater than those in the single administration. In conclusion, flutamide should be examined for efficacy and safety using doses of 375 to 1, 125 mg/day in the phase II study.

1)内分泌療法未治療の前立腺癌症例に対し, 375mg/日の用量で単独療法として使用しえる。この際, testosterone産生阻害療法に比し, 「生活の質」が保たれる。2)内分泌療法再燃例に対しても, ある程度その効果が期待できる。3)フルタミドと他の精巣性testosterone阻害剤との併用で, その併用効果が期待できる。4)また, LH-RHアナログの投与によるflare-up現象をフルタミドを併用することにより予防することが可能である, The phase II study of flutamide, a pure anti-androgen, was performed to estimate the clinical doses on 165 hormone untreated or treated patients with prostatic cancer. The hormone-untreated patients were given orally flutamide of 90, 375, 750 or 1, 125 mg/day in three divided doses daily for 12 weeks. Responses were not observed at the 90 mg/day dose except for improvement of clinical symptoms. However, an objective response rate of 48.8-46.7% was obtained at 375-1, 125 mg/day doses. In hormone-treated patients including cases refractory to the previous hormonal treatment, the objective response rates were 13.3 and 8.3% in 375 and 750 mg/day flutamide groups, respectively. Side effects such as gynecomastia, nausea, vomiting, diarrhea, and abnormal laboratory findings such as the elevation of hepatic transaminases were observed. The incidence increased dose-dependently. Determinations of serum hormone levels revealed an increase in testosterone levels by the use of flutamide. In conclusion 375 mg/day of flutamide is the optimal dose in monotherapy for hormone-untreated patients with prostatic cancer, where the quality of life can be maintained compared with therapies involving testosterone suppression. This dose is also expected to show some efficacy in cases refractory to hormone treatment.